ChemInform Abstract: Ag-Catalyzed Diastereo- and Enantioselective Synthesis of β-Substituted Tryptophans from Sulfonylindoles.

ArticleinOrganic Letters 12(8):1688-91 · March 2010with9 Reads
DOI: 10.1021/ol100161n · Source: PubMed
The asymmetric catalytic synthesis of beta-substituted tryptophan derivatives was realized in high diastereo- and enantioselectivity by the reaction of glycine derivatives with sulfonylindoles in the presence of catalyst derived from AgCl and a commercially available chiral monodentate phosphoramidite ligand. The resulting adduct was readily converted to beta-substituted tryptophan in 95% overall yield for two steps, which presented a highly efficient route to chiral beta-substituted tryptophan.
    • "On the other hand, non-racemic tryptophan derivatives were prepared with moderate stereoselectivities by F–C alkylation when ΔAla was incorporated into peptides (Gentilucci et al. 2010). Some asymmetric catalytic syntheses have been reported to afford with high levels of enantioselectivity (S)or (R)-tryptophans carrying a limited number of distinct modifications (Drury et al. 1998; Castle and Srikanth 2003; Zheng et al. 2010). Heck reaction between N-Ts-indoles and methyl 2-acetamidoacrylate furnished the dehydrotryptophans , whose asymmetric catalytic hydrogenation with [(COD)Rh(Et-DuPHOS] + TfO − as catalyst furnished enantiomerically pure (R)-5-and 6-substituted tryptophans (Prieto et al. 2009). "
    [Show abstract] [Hide abstract] ABSTRACT: Chiral dehydroamino acid building blocks are versatile starting materials for the preparation of optically active unusual amino acids and other compounds of pharmacological interest. Herein we disclose the expedient preparation of dehydroalanines (ΔAla) equipped with oxazolidin-2-one (Oxd) chiral auxiliaries, Ts-Oxd-ΔAla-OMe. These compounds have been obtained in high yields from dipeptides Ts-Ser/Thr/phenylSer-Ser-OMe by the one-pot cyclization-elimination reaction with N,N-disuccinimidyl carbonate and catalytic DIPEA. To test the efficacy of the chiral auxiliaries in controlling asymmetric transformations, the Friedel-Crafts alkylations of indoles carrying diverse substituents were performed in the presence of Lewis and Brønsted acids. The reactions proceeded with good to excellent diastereomeric ratios giving (S)- or (R)-tryptophan derivatives, isolated very conveniently by simple flash chromatography. To verify the utility of this approach, optically pure (S)-2-methyltryptophan and (S)-5-fluorotryptophan were obtained and utilized to prepare analogues of endogenous opioid peptide endomorphin-1, H-Tyr-Pro-Trp-PheNH2.
    Full-text · Article · Sep 2014
  • [Show abstract] [Hide abstract] ABSTRACT: A Brønsted base-catalyzed reaction of nitroalkanes with alkyl electrophiles provides indole heterocycles substituted at C3 bearing a sec-alkyl group with good enantioselectivity (up to 90% ee). Denitration by hydrogenolysis provides a product with equally high ee. An indolenine intermediate is implicated in the addition step, and surprisingly, water cosolvent was found to have a beneficial effect in this step, leading to a one-pot protocol for elimination/enantioselective addition using PBAM, a bis(amidine) chiral nonracemic base.
    Article · Dec 2010
  • [Show abstract] [Hide abstract] ABSTRACT: The title addition of glycine imines (I) to malonates (II) provides the Michael adducts (III) in high yields and moderate to good diastereo- and enantioselectivities.
    Article · Jan 2011
Show more